We have previously reported that the administration of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) to rats resulted in a significantly decreased serum thyroxine (T4), serum and pancreatic insulin levels, and hypoglycemia. Severe hormonal imbalance caused by low doses of TCDD could, in fact, be explained by effects on prolactin synthesis and secretion since prolactin is known to affect the development and function of endocrine organs such as the adrenal cortex, thyroid, pancreas and perhaps the adrenal medulla. In rats inoculated with a prolactin-secreting MtTW15 adenoma, increased serum prolactin resulted in a significantly decreased serum T4 concentration similar to the extent of reduction in response to TCDD administration. Prolactin has known effects on immune function, as does TCDD. We propose, therefore, to study the ability of TCDD to alter the circulating levels of major developmental and differentiative hormones. The serum prolactin levels will be monitored in rats at times after TCDD which coincide with the already demonstrated decreased body temperature and decreased serum T4. Circulating glucocorticoid levels will be measured as these hormones are known to feedback on prolactin secretion and thus regulate serum prolactin concentration. Catecholamines are major circulating trophic hormones which also may affect both prolactin and glucocorticoid levels as well as action. The effects of these hormones and their interactions to modify ornithine decarboxylase activity and RNA polymerase I activity in the liver of TCDD-treated rats will be assessed since a previous time-dependent effect of TCDD to alter the response of these enzyme activities to hormone stimulation or to partial hepatectomy has been observed in this laboratory. If detectable alterations in the regulation of one or more of these "stress-axis" hormones can be defined, we then will attempt to pinpoint the lesion to the appropriate endocrine organ(s) or to the hypothalamic nucleus involved in the regulation of the synthesis and secretion of the particular hormone. Industrial exposure, environmental exposure, and extensive animal experimentation have linked TCDD to severe toxic effects in both humans and animals. Environmental pollution with polychlorobiphenyls including TCDD mandates the necessity to attempt to pinpoint the underlying mechanism(s) of the toxicity of these substances.